New Drug Targeting Cancer Weakness Shows Great Promise

Main Category: Breast Cancer
Also Included In: Ovarian Cancer;  Prostate / Prostate Cancer;  Cancer / Oncology
Article Date: 25 Jun 2009 - 4:00 PDT

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Scientists at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital, working with pharmaceutical company AstraZeneca, have completed a Phase I clinical trial demonstrating the great promise of a completely new type of cancer treatment. The results are announced today in The New England Journal of Medicine.

Patients with inherited forms of advanced breast, ovarian and prostate cancers - caused by mutations in the BRCA1 and BRCA2 genes - were treated with the new drug olaparib (a PARP inhibitor). Despite having previously received many standard therapies, in more than half of the patients tumours shrank or stabilised. One of the first patients to be given the treatment is still in remission after two years.

Olaparib targets the cancer cells but leaves healthy cells relatively unscathed. Importantly, patients experienced very few side-effects and some reported the treatment was "much easier than chemotherapy".

Dr Johann de Bono, one of the ICR scientists who led the AstraZeneca/KuDOS-sponsored Phase I trial held at The Royal Marsden and the Netherlands Cancer Institute, said the positive results confirmed olaparib should be taken into larger patient trials.

"This drug showed very impressive results in shrinking patients' tumours," Dr de Bono says. "It's giving patients who have already tried many conventional treatments long periods of remission, free from the symptoms of cancer or major side-effects."

Olaparib is the first successful example of a new type of personalised medicine using "synthetic lethality", in which the treatment works in combination with a patient's own specific molecular defect. It was based on experiments conducted at the ICR and funded by Cancer Research UK and Breakthrough Breast Cancer showing that some cancers had an Achilles' heel: If drugs - such as olaparib - are used to block an enzyme called PARP in the body, the tumour cells' DNA breaks down and they die.

Cancer cells with the BRCA1 or BRCA2 mutations were the first discovered to be sensitive to PARP inhibitors, but there is evidence that olaparib will be effective in other cancers with different defects in the repair of DNA - this could include some non-inherited breast and prostate cancers and up to half of the most common type of ovarian cancer.

"This is a very important drug for the treatment of BRCA1/2-related cancer," ICR scientist and joint lead researcher Professor Stan Kaye, who is supported by Cancer Research UK, says. "The next step is to test this drug on other more common types of ovarian and breast cancers where we hope it will be just as effective."

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the ICR, developed the approach of targeting defects in DNA repair in cancer.

"We are delighted that the work we did in the lab has been translated so quickly into potential benefit for patients," Professor Ashworth says. "This concept is now being tested in a variety of clinical trials across the world."

Source
The Institute of Cancer Research